COMPUTATIONAL MODELING

Experimental studies to quantify the mechanical environment surrounding bone cells are challenging and as such computational and theoretical approaches have modelled either the solid or fluid environment of osteocytes to predict how these cells are stimulated in vivo. Osteocytes are composed of an elastic cell membrane that deforms in response to the external fluid flow imposed by mechanical loading. This represents a most challenging multi-physics problem in which fluid and solid domains interact and as such no previous study has accounted for this complex behaviour. Prof. McNamara’s group employ fluid-structure interaction (FSI) modelling to investigate the complex mechanical environment of osteocytes in vivo. Fluorescent staining of osteocytes is performed in order to visualise their native environment and develop geometrically accurate models of the osteocyte in vivo. These are the first computational FSI models to simulate the complex multi-physics
mechanical environment of osteocyte in vivo and provide a deeper understanding of bone mechanobiology.

Experimental and computational studies have sought to understand the role of bone composition and organisation in regulating the biomechanical behaviour of bone. However, due to the complex hierarchical arrangement of the constituent materials, the reported experimental values for the elastic modulus of trabecular and cortical tissue have conflicted greatly. Furthermore finite element studies of bone have largely made the simplifying assumption that material behaviour was homogeneous or that tissue variability only occurred at the microscale based on grey values from micro-CT scans.Prof. McNamara’s group have developed a three-scale finite element homogenisation scheme to enable prediction of homogenised effective properties of tissue level bone from its fundamental nanoscale constituents of hydroxyapatite mineral crystals and organic collagen proteins. This approach could provide a preclinical tool to predict bone mechanics following prosthetic implantation or bone fracture during disease.

Paper Overviews:

Osteocytes are believed to be the primary sensor of mechanical stimuli in bone, which orchestrate osteoblasts and osteoclasts to adapt bone structure and composition to meet physiological loading demands. Experimental studies to quantify the mechanical environment surrounding bone cells are challenging, and as such, computational and theoretical approaches have modelled either the solid or fluid environment of osteocytes to predict how these cells are stimulated in vivo. Osteocytes are an elastic cellular structure that deforms in response to the external fluid flow imposed by mechanical loading. This represents a most challenging multi-physics problem in which fluid and solid domains interact, and as such, no previous study has accounted for this complex behaviour. The objective of this study is to employ fluid-structure interaction (FSI) modelling to investigate the complex mechanical environment of osteocytes in vivo. Fluorescent staining of osteocytes was performed in order to visualise their native environment and develop geometrically accurate models of the osteocyte in vivo. By simulating loading levels representative of vigorous physiological activity ([Formula: see text] compression and 300 Pa pressure gradient), we predict average interstitial fluid velocities [Formula: see text] and average maximum shear stresses [Formula: see text] surrounding osteocytes in vivo. Interestingly, these values occur in the canaliculi around the osteocyte cell processes and are within the range of stimuli known to stimulate osteogenic responses by osteoblastic cells in vitro. Significantly our results suggest that the greatest mechanical stimulation of the osteocyte occurs in the cell processes, which, cell culture studies have indicated, is the most mechanosensitive area of the cell. These are the first computational FSI models to simulate the complex multi-physics mechanical environment of osteocyte in vivo and provide a deeper understanding of bone mechanobiology.

Experimental and computational studies have sought to understand the role of bone composition and organisation in regulating the biomechanical behaviour of bone. However, due to the complex hierarchical arrangement of the constituent materials, the reported experimental values for the elastic modulus of trabecular and cortical tissue have conflicted greatly. Furthermore finite element studies of bone have largely made the simplifying assumption that material behaviour was homogeneous or that tissue variability only occurred at the microscale based on grey values from micro-CT scans. Prof. McNamara’s group have developed a three-scale finite element homogenisation scheme to enable prediction of homogenised effective properties of tissue level bone from its fundamental nanoscale constituents of hydroxyapatite mineral crystals and organic collagen proteins. This approach could provide a preclinical tool to predict bone mechanics following prosthetic implantation or bone fracture during disease.